There is evidence that inflammatory mechanisms contribute to the progression of cardiovascular disease. Inflammatory markers, such as C-reactive protein (CRP) have been shown to predict future cardiovascular events. There are no studies that have examined the association of these markers to vascular dementia (VaD), a dementia that is closely associated with cerebrovascular events. To examine the association of early inflammatory activity to late age dementia, we conducted preliminary data analyses on already existing data from the Honolulu Heart Program (HHP) and its extension, the Honolulu-Asia Aging Study (HAAS). The HAAS is designed to examine risk factors for dementia and cognitive impairment. Since its start in 1991, we have clinically diagnosed 128 cases of Alzheimer's disease (AD), 58 cases of AD with concomitant cerebrovascular disease (mixed) and 107 cases of vascular dementia. Data on CRP were obtained on HHP cohort members as a part of a study on the relation of inflammation to the risk for incident stroke and myocardial infarction. For this study a random sample of 1,348 HHP participants was drawn and CRP determined. In this random control sample, 767 were also seen in the HAAS, including 30 cases of AD without any concomitant cerebrovascular disease, 10 cases of mixed dementia (AD with concomitant cerebrovascular disease), and 19 cases of vascular dementia. The preliminary results suggest men with high levels of CRP at baseline had a 2.84 (1.08-7.47) increased risk to develop vascular dementia 25 years later. This is consistent with the hypothesis that the inflammatory response reflects subclinical atherosclerotic processes, which in turn increases the risk for later clinical events. Additional samples from subjects who subsequently developed dementia (VaD and AD) will be analyzed to determine whether the findings are robust. We will also perform similar analyses using sample collected in the fourth exam as part of the NIA-funded objective to identify dementia cases. These additional analyses will provide insight into the short-term relation of CRP to the risk for dementia. The combination of the exam 2 and exam 4 results will allow us to identify individuals who have had a long-term exposure to higher levels of CRP and evaluate whether their risk for vascular dementia differs from those with less sustained exposure to high levels of CRP.